Coupling MgSO4-assisted SALLE with a fluorimetric turn-off strategy for the determination of cinacalcet HCl in pharmaceutical and human matrices

Abstract An innovative, sustainable analytical approach was developed by coupling an Epsom salt, E518 (magnesium sulfate)–facilitated salting-out assisted liquid–liquid extraction (SALLE) system with a safe molecular fluorescent probe, Celfia Pink B (CPB), employing a fluorescence turn-off sensing strategy. MgSO₄ acts as a green salting-out agent, enhancing phase separation efficiency and producing cleaner extracts with higher analyte recovery. CPB, a safe, food-grade dye, serves as a selective fluorogenic probe whose emission at 553 nm is quenched upon electrostatic ion-pair complex formation with Cinacalcet HCl under mildly acidic conditions. The method exhibited excellent linearity (0.08–1.3 µg/mL) with high sensitivity (LOD = 0.024 µg/mL; LOQ = 0.075 µg/mL). Validation according to ICH guidelines demonstrated robustness, precision, and accuracy across pharmaceutical formulations and biological matrices. Sustainability assessment using the WAC framework categorized the platform as “white,” highlighting low environmental impact, safe operation, and simplicity. By minimizing organic solvent use and eliminating hazardous reagents, this MgSO₄-assisted SALLE/fluorescence turn-off approach provides a green, highly sensitive, and versatile tool for trace-level determination of Cinacalcet HCl in pharmaceutical and biological matrices.